Process for making benzoxazepin compounds

摘要

Processes are described for the preparation of PI3K inhibitor, GDC-0032, Formula I, having the structure:;and intermediates useful for the preparation of I.

主权项

1. A process for preparing (2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide I, having the structure: and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, comprising: (a) reacting IV and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) to form 22 (b) reacting 22, a palladium catalyst, and III to form 23 (c) reacting 23 with an aqueous basic reagent to form II  and (d) reacting II with an acyl activating reagent, followed by ammonia to give I.